RESUMO
The trafficking of aquaporin 5 (AQP5) is critical for salivary secretion. Synaptosomal-associated protein 23 (SNAP23) is an important regulator in the process of membrane fusion. However, the role of SNAP23 on AQP5 trafficking has not been explored. Botulinum toxin type A (BoNT/A) is a bacterial toxin that effectively treats sialorrhea. We previously reported that BoNT/A induced AQP5 redistribution in cultured acinar cells, but the mechanism remained unclear. In this study, SNAP23 was predominantly localized to the plasma membrane of acinar cells in the rat submandibular gland (SMG) and colocalized with AQP5 at the apical membrane of acinar cells. In stable GFP-AQP5-transfected SMG-C6 cells, the acetylcholine receptor agonist carbachol (CCh) induced trafficking of AQP5 from intracellular vesicles to the apical membrane. Furthermore, SNAP23 knockdown by siRNA significantly inhibited CCh-induced AQP5 trafficking, whereas this inhibitory effect was reversed by SNAP23 re-expression, indicating that SNAP23 was essential in AQP5 trafficking. More importantly, BoNT/A inhibited salivary secretion from SMGs, and the underlying mechanism involved that BoNT/A blocked CCh-triggered AQP5 trafficking by decreasing SNAP23 in acinar cells. Taken together, these results identified a crucial role for SNAP23 in AQP5 trafficking and provided new insights into the mechanism of BoNT/A in treating sialorrhea and thereby a theoretical basis for clinical applications.
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Toxinas Botulínicas Tipo A , Sialorreia , Ratos , Animais , Toxinas Botulínicas Tipo A/farmacologia , Toxinas Botulínicas Tipo A/metabolismo , Aquaporina 5/genética , Aquaporina 5/metabolismo , Células Acinares , Sialorreia/metabolismo , Glândula Submandibular/metabolismoRESUMO
BACKGROUND: Myelodysplastic syndrome (MDS) is a complicated hematopoietic malignancy characterized by bone marrow (BM) dysplasia with symptoms like anemia, neutropenia, or thrombocytopenia. MDS exhibits considerable heterogeneity in prognosis, with approximately 30% of patients progressing to acute myeloid leukemia (AML). Single cell RNA-sequencing (scRNA-seq) is a new and powerful technique to profile disease landscapes. However, the current available scRNA-seq datasets for MDS are only focused on CD34+ hematopoietic progenitor cells. We argue that using entire BM cell for MDS studies probably will be more informative for understanding the pathophysiology of MDS. METHODS: Five MDS patients and four healthy donors were enrolled in the study. Unsorted cells from BM aspiration were collected for scRNA-seq analysis to profile overall alteration in hematopoiesis. RESULTS: Standard scRNA-seq analysis of unsorted BM cells successfully profiles deficient hematopoiesis in all five MDS patients, with three classified as high-risk and two as low-risk. While no significant increase in mutation burden was observed, high-risk MDS patients exhibited T-cell activation and abnormal myelogenesis at the stages between hematopoietic stem and progenitor cells (HSPC) and granulocyte-macrophage progenitors (GMP). Transcriptional factor analysis on the aberrant myelogenesis suggests that the epigenetic regulator chromatin structural protein-encoding gene HMGA1 is highly activated in the high-risk MDS group and moderately activated in the low-risk MDS group. Perturbation of HMGA1 by CellOracle simulated deficient hematopoiesis in mouse Lineage-negative (Lin-) BM cells. Projecting MDS and AML cells on a BM cell reference by our newly developed MarcoPolo pipeline intuitively visualizes a connection for myeloid leukemia development and abnormalities of hematopoietic hierarchy, indicating that it is technically feasible to integrate all diseased bone marrow cells on a common reference map even when the size of the cohort reaches to 1,000 patients or more. CONCLUSION: Through scRNA-seq analysis on unsorted cells from BM aspiration samples of MDS patients, this study systematically profiled the development abnormalities in hematopoiesis, heterogeneity of risk, and T-cell microenvironment at the single cell level.
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Genômica , Hematopoese , Síndromes Mielodisplásicas , Análise de Célula Única , Humanos , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Hematopoese/genética , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Células-Tronco Hematopoéticas/metabolismo , Microambiente Celular , Mutação/genéticaRESUMO
Hematopoietic stem cells (HSC) are primarily dormant in a cell-cycle quiescence state to preserve their self-renewal capacity and long-term maintenance. How HSC maintain the balance between activation and quiescence remains largely unknown. Herein, we found that phosphatase, Mg2+/Mn2+ dependent 1B (Ppm1b) is required for the expansion of phenotypic HSC in vitro. By using a conditional knockout mouse model in which Ppm1b was specifically depleted in hematopoietic cells, we demonstrated that loss of Ppm1b impaired the HSC homeostasis and hematopoietic reconstitution. Ppm1b deficiency mice also exhibited B-cell leukocytopenia, which is due to the compromised commitment and proliferation of B-biased lymphoid progenitor cells from common lymphoid progenitors. With the aid of a small molecular inhibitor, we confirmed the roles of Ppm1b in adult hematopoiesis that phenocopied the effects with loss of Ppm1b. Furthermore, transcriptome profiling of Ppm1b-deficient HSC revealed the disruptive quiescence of HSC. Mechanistically, Ppm1b interacted with ß-catenin and mediated its dephosphorylation. Loss of Ppm1b led to the decrease in the active ß-catenin (non-phosphorylated) that interrupted the Wnt/ß-catenin signaling in HSC, which consequently suppressed HSC expansion. Together, our study identified an indispensable role for Ppm1b in regulating HSC homeostasis via the Wnt/ß-catenin pathway.
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Células-Tronco Hematopoéticas , Homeostase , Camundongos Knockout , Proteína Fosfatase 2C , Via de Sinalização Wnt , Animais , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , Camundongos , Proteína Fosfatase 2C/metabolismo , Proteína Fosfatase 2C/genética , beta Catenina/metabolismo , HematopoeseRESUMO
BACKGROUND: Lactoferrin (LF) is an iron-binding multifunctional cationic glycoprotein. Previous studies have demonstrated that LF may be a potential drug for treating acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In this study, we explored the anti-inflammatory effect and mechanism of bovine lactoferrin (bLF) in ALI using the RNA sequencing (RNA-seq) technology and transcriptome analysis. METHODS AND RESULTS: Based on the differentially expressed genes (DEGs) obtained from RNA-seq of the Lung from mouse model, the bioinformatics workflow was implemented using the BGISEQ-500 platform. The protein-protein interaction (PPI) network was obtained using STRING, and the hub gene was screened using Cytoscape. To verify the results of transcriptome analysis, the effects of bLF on Lipopolysaccharide (LPS)-induced BEAS-2B cells and its anti-reactive oxygen species (ROS), anti-inflammatory, and antiapoptotic effects were studied via Cell Counting Kit-8 (CCK-8) test, active oxygen detection test, ELISA, and western blot assay. Transcriptome analysis revealed that two hub gene modules of DEGs were screened via PPI analysis using the STRING and MCODE plug-ins of Cytoscape. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these core modules are enriched in the PPAR (peroxisome proliferator-activated receptor) and AMPK (AMP-activated protein kinase) signaling pathways. Through cell experiments, our study shows that bLF can inhibit ROS, inflammatory reaction, and LPS-induced BEAS-2B cell apoptosis, which are significantly antagonized by the PPAR-γ inhibitor GW9662. CONCLUSION: This study has suggested that the PPAR-γ pathway is the critical target of bLF in anti-inflammatory reactions and apoptosis of ALI, which provides a direction for further research.
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Lesão Pulmonar Aguda , Lactoferrina , Animais , Camundongos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/genética , Anti-Inflamatórios/farmacologia , Apoptose , Lactoferrina/farmacologia , Lipopolissacarídeos , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment (TME) and can induce functional polarization of tumor macrophages. This study aimed to explore the effect of CAFs-derived exosome LINC01833 on the malignant biological behavior of non-small cell lung cancer (NSCLC) cells and its mechanism. Tumor tissues (n = 3) and adjacent noncancerous tissues (n = 3) were collected from patients with NSCLC, and fibroblasts (CAF, NF) were isolated from the two tissues. Expression of LINC01833/miR-335-5p/VAPA in NSCLC clinical tissues and cell lines was detected by RT-qPCR. Exosomes of CAFs and NFs were isolated by ultracentrifugation. Cell proliferation, migration, invasion, and M2 macrophage polarization were detected by MTT, transwell, wound-healing assay, and flow cytometry assay, while western blot was used to verify the expression of M2 macrophage polarization-related proteins. Tumor volume weight and M2 macrophage polarization were detected by tumor xenografts in nude mice. LINC01833 was highly expressed in NSCLC tumor tissues and cells. Knockdown of LINC01833 exosomes could significantly inhibit proliferation, migration, invasion of NSCLC cells, and M2 macrophage polarization of THP-1 cells, while simultaneous knockdown of miR-335-5p on the above basis could reverse the effect of knockdown of LINC01833. In vivo experiments also indicated that knockdown of LINC01833 exosomes suppressed tumor growth and M2 macrophage polarization. CAF-derived LINC01833 exosomes can promote the proliferation, migration and invasion of NSCLC cells and M2 macrophage polarization by inhibiting miR-335-5p and regulating VAPA activity.
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Fibroblastos Associados a Câncer , Carcinoma Pulmonar de Células não Pequenas , Exossomos , Neoplasias Pulmonares , Camundongos Nus , MicroRNAs , RNA Longo não Codificante , Animais , Feminino , Humanos , Masculino , Camundongos , Células A549 , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Exossomos/metabolismo , Exossomos/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Camundongos Endogâmicos BALB C , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismoRESUMO
OBJECTIVE: This study aimed to evaluate the differences in the accuracy of immediate intraoral, immediate extraoral, and delayed dental implant placement with surgical guides (static computer-aided implant surgery) in patients treated with mandibular reconstruction. METHODS: This was a retrospective study. The patients were divided into three groups: immediate intraoral placement (IIO), immediate extraoral placement (IEO), and delayed placement (DEL). Four variables were used to compare the planned and actual implant positions: angular deviation, three-dimensional (3D) deviation at the entry point of the implant, 3D deviation at the apical point of the implant, and depth deviation. RESULTS: The angular deviation was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .05) groups. The 3D deviation at the entry point was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .01) groups. The 3D deviation at the apical point was significantly higher in the IIO group than in the IEO (p < .01) and DEL (p < .01) groups. The depth deviation was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .05) groups. There was no statistical difference between the IEO and DEL group in angular and 3D deviation. CONCLUSION: With surgical guides, among the different approaches for implant placement, delayed implant placement remains the most accurate approach for patients treated with mandibular reconstruction.
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Implantes Dentários , Reconstrução Mandibular , Cirurgia Assistida por Computador , Humanos , Implantação Dentária Endóssea/métodos , Estudos Retrospectivos , Cirurgia Assistida por Computador/métodos , Desenho Assistido por Computador , Imageamento Tridimensional , Tomografia Computadorizada de Feixe CônicoRESUMO
OBJECTIVE: Patient-derived organoids are potent pre-chemotherapy models. Due to limited research on diverse types of oral squamous cell carcinoma (OSCC) and construction efficiency, our goal was to optimize OSCC organoid models from various sites and assess drug responsiveness. METHODS: We screened and optimized culture media, employing three-dimensional techniques to construct human-derived oral squamous cell carcinoma (OSCC) organoid models in vitro. Morphological validation, immunofluorescence analysis, tissue origin verification, and Short Tandem Repeat (STR) sequencing confirmed the consistency between organoids and source tissues. These organoid models were then subjected to varying concentrations of anticancer drugs, with subsequent assessment of cell viability to calculate IC50 values. RESULTS: Twenty-nine surgical specimens yielded an 86.2% success rate in culturing 25 organoids in vitro. Morphological consistency confirmed nuclear atypia and positive expression of K5, P40, and E-cadherin, indicating squamous epithelial origin. Cultured complex organoids included α-SMA+ tumour-associated fibroblasts and tumour stem cells expressing CD44 and Ki67. STR sequencing affirmed genomic homogeneity between cultured organoids and source tissues. Drug sensitivity testing revealed diverse responses among organoids, highlighting their value for assessing drug sensitivity. CONCLUSIONS: An efficient OSCC organoid culture system for personalized in vitro drug sensitivity screening was established, laying the foundation for precise treatment development.
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OBJECTIVES: To investigate soft-to-hard tissue response following mandibular reconstruction and to develop a predictive model for projecting soft tissue movement. MATERIALS AND METHODS: In this retrospective study, 18 patients receiving mandibular reconstruction using a vascularized iliac flap were enrolled. Various indicators for characterizing the movement of tissues were considered to identify the effective predictors for projecting soft tissue movements. Face-region-specific linear regression models for prediction were constructed and evaluated. RESULTS: The arithmetic mean of hard tissue movement in an extended area had the strongest correlation with the movement of the focal soft tissue, while the arithmetic mean in a regional area (Ram) was a more effective predictor. The linear regression model using Ram, global extrema and distances between them as the predictors performed the best in the lower margin of the face, with an average error of 1.51 ± 1.38 mm. Soft tissue movement in the alveolar process was not correlated with the existence of dentition, only can be predicted by the soft tissue movement below it. The area of the masseter was strongly correlation with Ram, but no other factors. CONCLUSIONS: An accurate prediction of soft tissue movements in the lower margin and the alveolar process of the face can be achieved by considering hard tissue and adjacent soft tissue movements. No effective predictor in the masseter area was identified. CLINICAL RELEVANCE: We investigated the relationship between hard tissue movements and the soft tissue responses in the facial area. Through building predictive models for projecting postoperative soft tissue movements, we derive insights for the aesthetic outcome of face surgeries. CLINICAL TRIAL REGISTRATION: This study was registered on the Chinese Clinical Trial Registry (registration number: ChiCTR2100054103).
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Ílio , Reconstrução Mandibular , Retalhos Cirúrgicos , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Ílio/transplante , Reconstrução Mandibular/métodos , Resultado do Tratamento , IdosoRESUMO
OBJECTIVE: This study aimed to investigate the features of bone mineral density (BMD) and cortical bone thickness in grafted fibula. MATERIALS AND METHODS: Eighty-six patients who underwent mandibular reconstruction using vascularized fibula flaps were enrolled, all of whom were followed up at 3, 6, and 12 months after surgery. The patients were grouped according to whether the condyle was preserved. BMD and cortical bone thickness were also measured. RESULTS: Condyle-preserved group consisted of 65 patients and condyle-unpreserved group consisted of 21 patients. There was a significant correlation between thickness and BMD, which was significantly correlated with follow-up time. One year after surgery, the BMD of the condyle-preserved group decreased from 1029.61 ± 156.01 mg/cm3 to 978.6 ± 141.90 mg/cm3, and thickness decreased from 3.29 ± 0.65 mm to 2.72 ± 0.72 mm. BMD of the condyle-unpreserved group decreased from 1062.21 ± 126.01 mg/cm3 to 851.26 ± 144.38 mg/cm3, and thickness decreased from 3.46 ± 0.89 mm to 2.56 ± 0.73 mm. In the condyle-preserved and unpreserved groups, the absorption rates of BMD were 3.29 ± 11.97% and 17.09 ± 12.42% at 12 months, respectively, and the rate of thickness was 20.7 ± 11.45% and 26.39 ± 12.23% at 12 months, respectively. CONCLUSION: BMD and thickness showed a decreasing trend over time. Preserving the condyle can slow bone resorption of the fibula. Regarding implant restoration, we recommend doctors to perform the treatment within 6-12 months after surgery in order to effectively manage bone resorption. CLINICAL RELEVANCE: Our study found that condylar preservation can decrease the absorption rate of BMD and cortical bone thickness, helping doctors make better clinical decisions. TRIAL REGISTRATION NUMBER: ChiCTR2300069661 (March 22, 2023).
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Densidade Óssea , Osso Cortical , Fíbula , Côndilo Mandibular , Reconstrução Mandibular , Humanos , Fíbula/transplante , Masculino , Feminino , Reconstrução Mandibular/métodos , Pessoa de Meia-Idade , Adulto , Osso Cortical/diagnóstico por imagem , Côndilo Mandibular/diagnóstico por imagem , Côndilo Mandibular/cirurgia , Idoso , Resultado do Tratamento , Retalhos CirúrgicosRESUMO
BACKGROUND: Treatment of human hypertrophic scar (HS) is a challenge for plastic surgeons, whereas the clinical and experimental research has been limited due to the lack of an ideal model of human HS tissue. OBJECTIVE: To establish a model of human HS using tissue engineering method, to improve the research for HS in the clinic and laboratory. METHODS: Hypertrophic scar fibroblasts (HSFBs) were transferred to polylactic acid (PLA)/polyglycolic acid (PGA) scaffolds. Biocompatibility of HSFBs-PLA/PGA composites was evaluated using scanning electron microscopy. Composites of HSFBs-PLA/PGA were implanted in subcutaneous pockets in athymic mice after 4 weeks in vitro culture. A re-entry operation was performed to obtain the HS-like tissues after 12 weeks of in vivo culture. The histological stain, the expression of type I collagen, the proliferation ability, and vitality of HSFBs were compared between human HS tissue and HS-like tissue. RESULTS: The structure of PLA/PGA scaffolds facilitates HSFBs adhesion and proliferation. The HSFBs-PLA/PGA composites were in vivo cultured for 12 weeks, and then HS-like tissues were harvested from nude athymic mice. There was no statistical significance in the expression of type I collagen, cell cycle, and cell proliferation between human HS tissue and HS-like tissue. CONCLUSION: The authors successfully established a model of human HS using the tissue engineering method, which could provide HS-like tissue for research. And it also could provide enough HS-like tissues to help reduce experimental variability within groups. This model can be used to investigate in prevention and treatment of HS and further explore the mechanisms of HS.
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Cicatriz Hipertrófica , Camundongos , Animais , Humanos , Colágeno Tipo I , Engenharia Tecidual , Camundongos Nus , Poliésteres , Fibroblastos , Alicerces TeciduaisRESUMO
BACKGROUND/AIM: There is no thorough overview of intentional tooth replantation techniques. We performed a bibliometric analysis of the development of intentional tooth replantation. MATERIALS AND METHODS: A comprehensive search of the Web of Science and SCOPUS databases was conducted in February 2023. Original articles and reviews of human studies with "intentional replantation" or synonyms in the titles, abstracts, or keywords were included. A descriptive analysis of bibliographic data, co-occurrence analysis, and coupling of publications was performed. Multivariate analysis was used to explore the bibliometric parameters associated with the citation counts. RESULTS: The study included 171 papers, which were co-authored by 500 individuals affiliated with 217 institutions from 28 countries/regions. The USA contributed the greatest number of publications, followed by China, and Japan. The USA had 694 citations, followed by Japan (210), and Turkey (210). The Journal of Endodontics and Dental Traumatology contributed the most citations. Five directions for future research were identified based on the coupling relationships of publications, including "managing vertical root fractures with adhesive resin using the intentional replantation technique," "intentional replantation for periodontally hopeless or endodontically compromised teeth," "intentional replantation for treating abnormalities of morphological development," "outcomes and prognosis factors of intentional replantation," and "treating root replacement resorption by intentional replantation." Multivariate analysis showed that the publication year, Journal Citation Reports ranking of journals, study design, and disease type were predictors of citation counts. CONCLUSIONS: This bibliometric analysis provides a comprehensive description of the intentional replantation technique. The USA published the greatest volume of papers and generated the most citations. The Journal of Endodontics and Dental Traumatology are considered the most influential. The Journal Citation Reports journal ranking (Q1, Q2), study design (case reports, cohort studies), and disease type (crown root fractures) were associated with the citation counts.
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Reimplante Dentário , Humanos , Bibliometria , Fraturas Ósseas , Reabsorção da Raiz , Fraturas dos Dentes , Reimplante Dentário/métodosRESUMO
OBJECTIVES: The aim of this study is to profile the transcriptional landscapes of affected tissues and peripheral blood mononuclear cells (PBMCs) at the single-cell level in IgG4-related disease (IgG4-RD). Identifying the cell populations and crosstalk between immune cells and non-immune cells will assist us in understanding the aetiology of IgG4-RD. METHODS: We performed single-cell RNA sequencing analysis on submandibular glands (SMGs) and PBMCs from patients with IgG4-RD and matched controls. Additionally, bulk RNA sequencing of PBMCs was used to construct the immune repertoire. Furthermore, multiplex immunofluorescence staining was performed to validate the transcriptomic results. RESULTS: We identified three novel subsets of tissue-resident immune cells in the SMGs of patients with IgG4-RD. TOP2A_B cells and TOP2A_T cells had stemness signatures, and trajectory analysis showed that TOP2A_B cells may differentiate into IgG4+plasma cells and that TOP2A_T cells may differentiate into T follicular helper (Tfh) cells. ICOS_PD-1_B cells with Tfh-like characteristics appeared to be an intermediate state in the differentiation from B cells to IgG4+plasma cells. The cellular communication patterns within immune cells and between immune cells and non-immune cells were altered in IgG4-RD compared with controls. Consistently, infection-related pathways were shared in B cells and T cells from SMGs and PBMCs. Furthermore, immune clonotype analysis of PBMC samples showed the complementary determining region 3 amino acid CQQSYSTPYTF was expanded in patients with IgG4-RD. CONCLUSION: Our data revealed the cellular and molecular changes at the single-cell resolution of IgG4-RD and provide valuable insights into the aetiology and novel therapeutic targets of the autoimmune disease.
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Doença Relacionada a Imunoglobulina G4 , Humanos , Doença Relacionada a Imunoglobulina G4/genética , Leucócitos Mononucleares , Glândula Submandibular , Análise da Expressão Gênica de Célula Única , Imunoglobulina GRESUMO
OBJECTIVE: Intraglandular injection of botulinum toxin type A (BoNT/A) effectively treats sialorrhea. Myoepithelial cells (MECs) are essential for salivary secretion. The role of MECs in BoNT/A-inhibited salivary secretion, and its underlying mechanisms remain unknown. MATERIALS AND METHODS: BoNT/A was injected into rat submandibular glands (SMGs). At 1, 2, 4, 8, and 12 weeks postinjection, salivary flow rate of SMGs was measured. Electron microscopy, immunohistochemistry, immunofluorescence, and Western blot analysis were used to detect morphological and functional changes in MECs and chemical denervation in SMGs. RESULTS: BoNT/A temporarily decreased salivary secretion in rat SMGs and this inhibitory effect lasted 4 weeks. During the inhibitory period, MECs atrophied and expressed reduced α-smooth muscle actin (α-SMA), vimentin, and phosphorylated myosin light chain 2 (p-MLC2), suggesting that BoNT/A attenuated MEC contractility. Furthermore, BoNT/A cleaved synaptosome-associated protein 25 (SNAP-25) and decreased the expression and activity of acetylcholinesterase (AChE), indicating that BoNT/A-induced chemical parasympathetic denervation of SMGs by cleaving SNAP-25. CONCLUSIONS: BoNT/A temporarily caused MEC atrophy and decreased MEC contractility in rat SMGs, which contributed to reversible inhibition of salivary secretion. The underlying mechanisms involved temporary parasympathetic denervation caused by SNAP-25 cleavage. These findings provide new insights into the mechanisms of BoNT/A-inhibited salivary secretion.
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OBJECTIVES: Tight junctions (TJs) are involved in the regulation of salivary secretion via paracellular pathway. Botulinum toxin type A (BTXA) is widely used for the treatment of hypersecretion diseases such as sialorrhea. This study aimed to investigate the role of TJs in BTXA-inhibited secretion of the submandibular gland (SMG). MATERIALS AND METHODS: BTXA was injected into the SMGs of rats, and the same amount of saline was injected as a control. Western blot, real-time PCR, and immunofluorescence staining were used to detect the expression and distribution of TJ proteins. Paracellular permeability was evaluated using the transepithelial electrical resistance (TER) measurements and fluorescent tracer detection in BTXA-stimulated SMG-C6 cells. RESULTS: BTXA injection into the SMGs of rats led to increased expression of claudin (Cldn) -1 and Cldn3. Immunofluorescence staining showed no significant changes in the distribution of TJ proteins. In vitro, BTXA increased the TER values and significantly reduced the permeability of fluorescent tracer, suggesting that BTXA decreased the paracellular permeability. The expression levels of Cldn1, Cldn3, and Cldn4 were upregulated after BTXA treatment. CONCLUSION: The expression of TJ proteins changed in both animal models and SMG-C6 cells after BTXA treatment, which may contribute to the inhibition of salivary secretion.
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Toxinas Botulínicas Tipo A , Junções Íntimas , Ratos , Animais , Junções Íntimas/fisiologia , Toxinas Botulínicas Tipo A/farmacologia , Toxinas Botulínicas Tipo A/metabolismo , Salivação , Glândula Submandibular/metabolismoRESUMO
OBJECTIVE: To explore the effect of early swallowing training on postoperative outcomes of patients who had undergone oral cancer surgery plus free flap reconstruction. SUBJECTS AND METHODS: In this prospective, randomized controlled trial, 121 patients who had undergone oral cancer surgery plus free flap reconstruction were randomly assigned to the control (n = 59) or intervention group (n = 62). The control group underwent routine nursing measures. The intervention group received swallowing training on the sixth postoperative day. On the 15th day and 1 month after surgery, the swallowing function (Mann Assessment of Swallowing Ability-Oral Cancer [MASA-OC] score), weight loss rate, time of nasogastric tube removal, and quality of life were evaluated. RESULTS: Patients in the intervention group had higher MASA-OC scores and better weight loss rates than those in the control group on the 15th day (MASA-OC: p = 0.014, weight loss: p < 0.001) and 1 month (both p < 0.001) after surgery. The time of nasogastric tube removal and the quality of life was statistically significant between groups (p < 0.001). CONCLUSION: Early swallowing training improves the swallowing function, nutritional status, and quality of life and shortens the indwelling time of nasogastric tube of patients who have undergone oral cancer surgery plus free flap reconstruction.
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OBJECTIVES: To reveal the change patterns of the facial soft tissue after applying mandibular reconstruction. MATERIALS AND METHODS: 16 Patients with mandibular benign tumor were recruited in this retrospective study. For all patients, segmental mandibular osteotomy and concurrent reconstruction using vascularized iliac flap were conducted. The soft tissue thickness of patients' lower face was measured with CT scans before surgery, 1 week, 6 months and 1 year after surgery. The time-dependent changes of tissue thickness were analyzed. RESULTS: The most significant tissue swelling was 28.86%, at 1 week after the surgery. The average increase of tissue thickness was 4.78 ± 5.30 mm across patient. After 1 year of the surgery, tissue thickness decreased to the level before operation or the level of the healthy side. The thickness of the low-density tissue fluctuated mildly, while the thickness of the high-density tissue fluctuated significantly. The disuse atrophy of the masseter occurred 1 week after the surgery, and was reversed after 1 year. The removal of the submandibular gland caused depression in submandibular area, which intensified over time. CONCLUSION: Across patients, soft tissue thickness in the lower face after mandibular osteotomy and reconstruction increased significantly 1 week after the surgery, and decreased over time. After 1 year, tissue thickness went back to the pre-surgery level, where matched up with the healthy side. CLINICAL RELEVANCE: We documented the change patterns of the facial soft tissue after mandibular reconstruction. These results can help improve the planning of virtual surgeries and the timing for aesthetic assessment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ChiCTR2100054103.
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Neoplasias Mandibulares , Reconstrução Mandibular , Humanos , Reconstrução Mandibular/métodos , Estudos Retrospectivos , Estética Dentária , Retalhos Cirúrgicos , Mandíbula/cirurgia , Neoplasias Mandibulares/patologia , Transplante Ósseo/métodosRESUMO
OBJECTIVE: The study aims to compare differences among iliac bone flaps with different iliac crest orientations for the repair of mandibular defects with an aim to analyze their advantages, disadvantages, and effects. MATERIAL AND METHODS: Clinical data and computed tomography scans of all patients who underwent iliac bone flap repair of the mandible in Peking University School and Hospital of Stomatology from January 2016 to April 2021 were collected. Patients were divided into the iliac crest towards alveolar process (Group A) and the iliac crest towards mandibular inferior margin (Group B). Software was used to measure corresponding indicators. The results obtained for the groups were statistically analyzed. RESULTS: The study included 78 patients (25 and 53 in groups A and B, respectively). The symmetry of the LC-type defect was better in group A (p < 0.05). The all-bone width of the alveolar process side in group A was greater than 6 mm; in 15 cases of group B, the width was less than 6 mm (p < 0.05). The intermaxillary distance of two sites were higher in group B (p < 0.05). The bone cortical thickness was significantly thicker in group A (p < 0.05). CONCLUSION: One year after the mandibular body defect was reconstructed with a vascularized iliac bone flap, the iliac crest towards alveolar process group showed better bone symmetry, width, intermaxillary distance, and cortical thickness to meet the planting requirements. CLINICAL RELEVANCE: The use of an iliac crest towards alveolar process may be a better approach for mandible reconstruction.
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Mandíbula , Reconstrução Mandibular , Retalhos Cirúrgicos , Humanos , Transplante Ósseo/métodos , Ílio , Mandíbula/cirurgia , Neoplasias Mandibulares , Reconstrução Mandibular/métodos , Implantes DentáriosRESUMO
Facial nerve trauma occasionally develops during oral and maxillofacial surgery. This study was aimed at enhancing the available knowledge on facial nerve reanimation correlated to surgery and proposing our surgical algorithm. We retrospectively analyzed medical records of patients who underwent facial reanimation surgery at our hospital. The inclusion criterion was surgery for facial reanimation from January 2004 to June 2021. We included 383 eligible patients who underwent facial reanimation surgery. Trauma or maxillofacial neoplasms were noted in 208 of 383 and 164 of 383 cases, respectively. In 238 of 383 cases, nerve branches were likely more vulnerable. Facial nerve anastomosis was performed in 256 patients. Sixty-eight patients received nerve grafts. In 22 patients, distal facial nerve transfer to the masseteric nerve, sublingual nerve, or contralateral facial nerve was performed. Twenty-five patients received static surgery; in most cases, the temporalis fascia flap (20/25) was used. The nerve function outcomes were HB grade I (n=17), Grade â ¡ (n=108), Grade â ¢ (n=118), Grade â £ (n=94), and Grade V (n=46). The mean follow-up time was 4.88 ± 3.93 years. Facial paralysis caused by trauma ( P =0.000), branch injury ( P =0.000), and the primary reconstruction of facial nerve ( P =0.000) were predictive of favorable treatment outcomes. Although facial nerve injury caused by trauma was more likely, cases of interference in facial expression could be limited, and so did the injury to branches. Nerve anastomosis was prioritized if a tension-free suture was possible. Maintaining the integrity of the nerve and shortening the duration of mimetic muscular denervation were crucial.
Assuntos
Traumatismos do Nervo Facial , Paralisia Facial , Transferência de Nervo , Procedimentos de Cirurgia Plástica , Humanos , Paralisia Facial/etiologia , Nervo Facial/cirurgia , Estudos Retrospectivos , Traumatismos do Nervo Facial/cirurgia , Traumatismos do Nervo Facial/complicaçõesRESUMO
PURPOSE: To investigate the clinical characteristics of oral and maxillofacial tumors in children and adolescents. METHODS: This is a retrospective study of patients who had oral and maxillofacial tumors under the age of 18 years and were treated at the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from January 1990 to July 2021 (31 y). Their general conditions, pathological diagnosis, gender, age, and anatomical location were counted to analyze their morbidity and composition characteristics. RESULTS: This study contained 5405 cases, including 2903 male patients and 2502 female patients, with a median age of 9 years. Peak incidence was observed in the 14 to 18 years age group. The mandible (22.15%), maxilla (11.75%), and tongue (9.25%) were the most common sites of incidence. Malignant and intermediate type tumors accounted for 13.04%, benign tumors and tumor-like lesions for 55.67%, most often occurs in the maxillofacial bone, of which fibro-osseous lesions constitute an important part. Cysts accounted for 31.29%. Among the tumors occurring in the jaws, the most common malignant type was sarcoma, and ameloblastoma was the most common benign tumor. Malignant jaw tumors were mostly treated by resection, 10.64% by fibular flap reconstruction. While benign jaw tumors and tumor-like lesions were mostly treated by resection or curettage. CONCLUSIONS: The distribution of anatomical location and pathological types of oral and maxillofacial tumors in children has certain characteristics, so that the selection of their treatment options is different from that of adults due to the consideration of the growth and developmental characteristics of children.
Assuntos
Ameloblastoma , Neoplasias Maxilomandibulares , Neoplasias de Tecidos Moles , Cirurgia Bucal , Adulto , Humanos , Criança , Masculino , Feminino , Adolescente , Estudos Retrospectivos , Neoplasias Maxilomandibulares/epidemiologia , Neoplasias Maxilomandibulares/cirurgia , Neoplasias Maxilomandibulares/diagnóstico , Ameloblastoma/epidemiologia , Ameloblastoma/cirurgiaRESUMO
BACKGROUND: This retrospective study reviewed all patients who underwent oral and maxillofacial reconstruction with fibular flaps in the last 2 decades at a single hospital. MATERIALS AND METHODS: We reviewed all patients with fibular flaps from 1999 to 2018. The following data were collected: sex; age; reconstruction region; diagnosis; the number of days spent in the hospital after surgery; time spent using a tourniquet for harvesting a fibula flap; vessels at the recipient site; the prevalence of unplanned reoperations; the prevalence of flap failure; history of preoperative radiotherapy; virtual surgical planning; segments of the fibula. RESULTS: In total, 2640 patients were included. The mean age was 45.5 years. The most prevalent region of reconstruction was the mandible (n=2347, 88.9%). The most common diagnosis was squamous cell carcinoma (n=1057, 40.0%). The mean number of days spent in the hospital after surgery decreased year-by-year from 18.3 days to 10.4 days. The first choice of recipient artery was the facial artery (n=1643, 62.2%) and that of the recipient vein was the external jugular vein (n=1196, 45.3%). The prevalence of surgical success was 97.6%. Prevalence of unplanned reoperations was 7.5%. CONCLUSIONS: The fibular flap was a good choice for oral and maxillofacial bony reconstruction in most cases.